HIV(+) women have significantly elevated incidence of cervical pre-cancer (i.e., CIN-2/CIN-3) and cancer, and at each clinical visit nearly a third (25%-35%) have abnormal Pap tests (i.e., ASC-US+). Most of these abnormal Paps do not, however, reflect clinically relevant disease (i.e., CIN-2+). Thus, most cervical colposcopy/biopsy are conducted unnecessarily at great expense to the health care system, as well as risk of bleeding, pain, infection, and anxiety among HIV(+) women - which are defined as harms by USPHS/CDC. Encouragingly, a new era of molecular screening has begun with several promising, commercially available, cervical cancer screening assays with good sensitivity, specificity, positive (PPV), negative predictive value (NPV), either alone or as an adjunct to Pap, in HIV(-) women. However, it is unknown if these assays (listed below) are useful in HIV(+) women - patients in great need of more accurate cervical cancer screening. Therefore, the proposed study will for the first time determine the sensitivity/specificity/PPV/NPV of promising molecular cervical cancer screening methods in HIV(+) women. It will involve 1,050 subjects, including N=400 new HIV(+) enrollees in the Women's Interagency HIV Study (WIHS), the largest cohort of HIV(+) women in the US, and N=650 HIV(+) women who will be separately enrolled through WIHS-affiliated colposcopy clinics. Colposcopy patients are typically referred because of an abnormal Pap and, thus, their data can be used to study new assays as an adjunct to Pap tests (Aim 1). However, we also wish to study the sensitivity/specificity/PPV/NPV of each individual molecular assay in HIV(+) women, as well as assess these assays in combination with one another (Aim 2). By adjusting for sampling fractions (e.g., oversampling of women with abnormal Paps), we can combine data from the new WIHS recruits and colposcopy patients to accurately estimate the results that would be obtained in a several-fold larger primary screening population (see C.3.) - a cost effective design. The proposed molecular assays include (i) two FDA-approved DNA tests for oncogenic HPV namely, the cobas HPV Test and Hybrid Capture 2 (HC2), (ii) cellular markers of E6 activity / proliferation (p16/ki-67 cytology; CINtec+), (iii) cellular markers of aberrant S-phase induction (MCM2/Top2A cytology; BD ProExC), (iv) oncHPV E6/E7 oncogene mRNA expression (PreTect HPV-Proofer), and (v) an in-houseHPV DNA PCR that provides semi-quantitative results for >40 individual HPV types. All Paps and histology will be reviewed by an expert pathology panel, and all assays will be centrally conducted. If as predicted the accuracy of cervical cancer screening is improved through the use of one or more of these promising molecular assays it could change clinical practice in HIV(+) women.